Adherence to oral anticancer hormonal therapy in breast cancer patients and its relationship with treatment satisfaction: an important insight from a developing country.

BACKGROUND: Hormone-positive breast cancer is the most common type and represents a burden in all countries. Treatment satisfaction might be a predictor for adherence, as higher satisfaction with medication encourages patients to adhere appropriately to the medication and, consequently, successfully achieve the treatment goals. The present study evaluated the adherence of women with hormone-positive breast cancer to oral hormonal drugs and correlated it with treatment satisfaction and other sociodemographic and clinical factors. METHODS: A cross-sectional design was applied. This study included two cancer centers. Data were collected from patients through face-to-face interviews and medical record reviews. The Medication Adherence Scale was adapted to assess medication adherence, and the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4 was adopted to measure treatment satisfaction. RESULTS: The final analysis included 106 patients, with a mean age ± SD of 51.9 ± 1.2. Approximately 35% were hospitalized in the past year. Current hormonal therapy among cancer patients included letrozole (38.7%), tamoxifen (31.1%), exemestane (17%), and anastrozole (13.2%). The median adherence score was 5.0 [4.8-6.0], and 62.3% adhered fully to their oral hormonal drugs in the past week. The median scores of effectiveness, side effects, convenience, and global satisfaction were 66.67 [61.11.0-72.22], 75.00 [48.44-100.00], 66.67 [66.67-72.22], and 71.43 [57.14-78.57], respectively. A significantly lower adherence score was identified in patients living in camps (p = 0.020). Patients with comorbidities and those who continued on the same hormonal therapy had higher adherence scores, although they were not statistically significant. Multiple linear regression analysis showed that two domains of treatment satisfaction, side effects (p = 0.013) and global satisfaction (p = 0.018), were predictors of adherence to oral hormonal drugs. CONCLUSIONS: The current study revealed a significant association between treatment satisfaction and adherence to oral hormonal therapy. We recommend creating a specialized scale to measure adherence, considering the psychosocial factors that affect hormonal anticancer medication adherence.

Androgen Receptor in Hormone Receptor-Positive Breast Cancer.

Breast cancer subtypes expressing hormone receptors (HR+ BCa) have a good prognosis and respond to first-line endocrine therapy (ET). However, the majority of HR+ BCa patients exhibit intrinsic or acquired ET resistance (ET-R) and rapid onset of incurable metastatic BCa. With the failure of conventional ET, limited targeted therapy exists for ET-R HR+ BCa patients. The androgen receptor (AR) in HR-negative BCa subtypes is emerging as an attractive alternative target for therapy. The AR drives Luminal AR (LAR) triple-negative breast cancer progression, and LAR patients consistently exhibit positive clinical benefits with AR antagonists in clinical trials. In contrast, the function of the AR in HR+ BCa is more conflicting. AR in HR+ BCa correlates with a favorable prognosis, and yet, the AR supports the development of ET-R BCa. While AR antagonists were ineffective, ongoing clinical trials with a selective AR modulator have shown promise for HR+ BCa patients. To understand the incongruent actions of ARs in HR+ BCa, the current review discusses how the structure and post-translational modification impact AR function. Additionally, completed and ongoing clinical trials with FDA-approved AR-targeting agents for BCa are presented. Finally, we identify promising investigational small molecules and chimera drugs for future HR+ BCa therapy.

Neoadjuvant chemotherapy use trends among older women with breast cancer: 2010-2017.

PURPOSE: This study assessed chemotherapy use trends before (neoadjuvant chemotherapy [NAC]) or after surgery (adjuvant chemotherapy [AdC]) among older women with breast cancer and examined factors related to NAC receipt. METHODS: Women (> 65 years) diagnosed with stage I-III breast cancer during 2010-2017 who received NAC or AdC were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. All patients were stratified into six strata based on subtype (hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR + /HER2-], HER2 + , and triple-negative breast cancer [TNBC]) and stage (I-II and III). Cochran-Armitage tests were performed to test temporal trends of NAC use in each stratum. Multivariable logistic regression analyses were performed to identify factors (sociodemographic and clinical) related to NAC use. RESULTS: Among included older (mean ± standard deviation: 72.3 ± 5.2 years) women (N = 8,495) with stage I-III breast cancer, NAC use increased from 11.7% (2010) to 32.6% (2017). Significant increases in NAC were found in all strata (p < .0001) with more substantial increases in HER2 + disease and TNBC compared to HR + /HER2- disease. Multivariable logistic regressions identified the youngest age category (66-69 years) and later stage as significant (p < 0.05) predictors of NAC receipt in most strata, in addition to diagnosis year. CONCLUSION: Similar to the overall breast cancer population, NAC use increased among a population of older women. NAC was received by most patients with stage III HER2 + disease or TNBC in more recent years and was more common among younger elderly women and those in stage III.

Impact of body mass index on the efficacy of aromatase inhibitors in patients with metastatic breast cancer.

PURPOSE: Higher levels of estrogen in obese patients may lead to incomplete inhibition by aromatase inhibitors (AIs). The aim of this study was to determine the impact of body mass index (BMI) on efficacy of AIs in patients with metastatic hormone receptor (HR)-positive breast cancer (BC). METHODS: We performed a retrospective chart review of all female patients with metastatic HR-positive BC on an AI in first- or second-line settings and seen at our academic institution between 2001 and 2020. The primary endpoint was progression-free survival (PFS), defined as the time from start of AI to disease progression or death from any cause. RESULTS: We identified 219 patients who had received an AI in the first- or second-line settings for metastatic HR-positive BC and with documented information on BMI. Of the 219 patients, 56% (123) had a low BMI (defined as < 27 kg/m2) and 44% (96) had a high BMI (≥ 27 kg/m2). The median PFS was 21.9 months (95% CI 14.5 to 28.4) in the low BMI group versus 20.2 months (95% CI 14.3 to 27.5) in the high BMI group (p = 0.73). CONCLUSION: While BMI influences efficacy of AIs in the adjuvant setting, our results suggest that in the metastatic setting, BMI may not impact the efficacy of AIs. This discrepancy could be due to other differences in disease characteristics that make complete aromatase inhibition more important in the adjuvant setting when disease burden is the lowest.

The experiences and perceptions of female breast cancer patients regarding weight management during and after treatment for oestrogen-receptor positive disease: a qualitative study.

BACKGROUND: Weight gain is commonly observed during and after breast cancer treatment and is associated with poorer survival outcomes, notably in women with oestrogen-receptor positive disease. The aim of this qualitative study was to investigate the experiences and perceptions of oestrogen-receptor positive (ER +) female breast cancer patients (BCPs) regarding weight management behaviours during and after treatment. Secondly, to gain insight into the experiences of healthcare professionals (HCPs) regarding the provision of weight management advice to patients undergoing treatment. METHODS: Four focus groups involving 16 BCPs having a median (range) age of 51 (35-70 y) and three focus groups involving 21 HCPs aged 46 (29-62) were held at a university campus, local cancer support centre or clinical site. Data were analysed using Framework analysis. RESULTS: Four overarching themes (and 10 subthemes) were identified: (1) Treatment; (2) Support for lifestyle behaviour change; (3) Information availability for BCPs; (4) Knowledge of current evidence amongst HCPs. The physical and psychological consequences of treatment influenced motivation for weight management amongst BCPs. Social support for health promoting behaviours was viewed as important but was conflicting, requiring context-specific considerations. BCPs said they would have welcomed access to credible information (guided by HCPs) about the potential detrimental health effects of excess body weight and weight gain, together with advice on weight management via healthy eating and physical activity. HCPs felt that they had insufficient knowledge of public health dietary and physical activity recommendations or evidence-based interventions to confidently offer such advice. HCPs expressed concern that raising weight management issues would exacerbate distress or invoke feelings of guilt amongst BCPs, and cited time pressures on patient consultations as additional barriers to providing weight management support. CONCLUSION: The study yielded novel insights into factors influencing weight management behaviours amongst overweight ER + BCPs. The results suggest that evidence-based information and support, which addresses key physical and psychological challenges to physical activity and dietary behaviours, offers the best route to sustainable weight management in this population.

Abemaciclib: The First FDA-Approved CDK4/6 Inhibitor for the Adjuvant Treatment of HR+ HER2- Early Breast Cancer.

OBJECTIVE: To review the new indication of cyclin-dependent kinase (CDK4/6) inhibitor abemaciclib for the adjuvant treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), axillary lymph node (LN) positive early breast cancer (EBC) at high risk of recurrence and a Ki-67 ≥20%. DATA SOURCES: A literature search was performed through PubMed, ClinicalTrials.gov, and Food and Drug Administration (FDA) website (February 1, 2018, to December 23, 2021) to identify relevant information. STUDY SELECTION AND DATA EXTRACTION: Human and animal studies related to pharmacology, pharmacokinetics, efficacy, and safety of abemaciclib were identified. DATA SYNTHESIS: Addition of abemaciclib to standard of care endocrine therapy (ET) for patients with high-risk clinicopathologic features and Ki-67 ≥20% demonstrated 30% reduction in the risk of developing invasive disease and distant recurrence. At 15.5 months, abemaciclib + ET demonstrated a significant improvement in invasive disease-free survival (IDFS) vs ET alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.93, P = 0.01). At 27 months, IDFS benefit was maintained (HR, 0.70; 95% CI, 0.59-0.82, P < 0.0001). Diarrhea occurred in more than 80% of patients in the abemaciclib arm. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review describes the clinical applicability of adjuvant abemaciclib for patients with HR+, HER2- EBC at high risk for recurrence. CONCLUSION: Adjuvant abemaciclib significantly reduces the risk for early development of invasive disease and distant recurrence in patients with HR+, HER2- node positive EBC. Longer follow-up is needed to determine the impact of adjuvant abemaciclib on late disease recurrence and survival outcomes.

Estrogen Receptor Alpha and ESR1 Mutations in Breast Cancer.

The estrogen receptor alpha (ERα) is a nuclear transcription factor that is expressed in more than 70% of all breast cancers. Key genes involved in proliferation and tumor progression are transcriptionally regulated by ERα making it an important therapeutic target. Indeed, the first class of targeted treatments in cancer are endocrine treatments that target ERα either by competitive inhibition, reduced ligand production or receptor degradation. Despite the efficacy of these drugs, resistance to endocrine treatment remains a key clinical challenge. Only about 50% of patients treated with endocrine treatment in early-stage disease will benefit from adjuvant endocrine treatment and nearly all patients treated in the metastatic setting will develop disease progression while on endocrine treatment. Multiple mechanisms of resistance to endocrine treatment have been identified in pre-clinical models and clinical samples. These include both intrinsic (de novo) mechanisms and adaptive, acquired mechanisms. Over the past few years, gain-of-function missense mutations of ESR1, the gene encoding ERα, have been unveiled and identified as the most common genomic mechanism of acquired resistance to endocrine treatments. These mutations are clustered in a "hot spot" region within the ligand binding domain and engender constitutive, ligand-independent activity. Clinical studies evaluating these ESR1 mutations in metastatic ERα positive breast cancer demonstrate decreased overall survival which also highlights their prognostic role. In this chapter, we will provide a detailed review of structural and biophysical characteristics, functional consequences and clinical implications of the ESR1 mutations. We will also discuss potential therapeutic strategies to overcome treatment resistance in the context of ESR1 mutations and implications for future treatment selection.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

BACKGROUND: We aimed to evaluate the efficacy of fulvestrant and its affecting clinical factors, including the optimal sequencing of fulvestrant and chemotherapy in a real-life cohort. METHODS: The data of 256 metastatic hormone-positive breast cancer patients treated with fulvestrant were evaluated. The association of clinical factors with survival was analyzed with Kaplan-Meier and Cox-regression analyses. RESULTS: The median age of patients was 57 years. More than half of the patients used fulvestrant in later lines and after chemotherapy (75.8%). The median progression-free (PFS) and overall survival (OS) of all cohort were 6.05 ± 0.56 and 29.70 ± 1.61 months, respectively. Primary endocrine resistance (HR: 1.989, 95% CI: 1.430-2.766, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p = 0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p = 0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p = 0.340), disease control rate (p = 0.076), and OS (p = 0.289) and PFS (p = 0.276) were similar to overall cohort. DISCUSSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy.

BACKGROUND: There is currently no clinical trial data regarding the efficacy of everolimus exemestane (EE) following prior treatment with CDK4/6 inhibitors (CDK4/6i). This study assesses the use and efficacy of everolimus exemestane in patients with metastatic HR+ HER2- breast cancer previously treated with endocrine therapy (ET) or endocrine therapy + CDK4/6i. METHODS: Retrospective analysis of electronic health record-derived data for HR+ HER2- metastatic breast cancer from 2012 to 2018. The proportion of patients receiving EE first-line, second-line, or third-line, and the median duration of EE prior to next line of treatment (TTNT) by line of therapy was calculated. OS for patients receiving EE first-line, second-line, or third-line, indexed to the date of first-line therapy initiation and stratified by prior treatment received, was calculated with Kaplan-Meier method with multivariable Cox proportional hazards regression analysis. RESULTS: Six hundred twenty-two patients received EE first-line (n = 104, 16.7%), second-line (n = 273, 43.9%) or third-line (n = 245, 39.4%). Median TTNT was 8.3 months, 5.5 months, and 4.8 months respectively. Median TTNT of EE second-line was longer following prior ET alone compared to prior ET + CDK4/6i (6.2 months (95% CI 5.2, 7.3) vs 4.3 months (95% CI 3.2, 5.7) respectively, p = 0.03). Similarly, EE third-line following ET alone vs ET + CDK4/6i in first- or second-line resulted in median TTNT 5.6 months (95% CI 4.4, 6.9) vs 4.1 months (95% CI 3.6, 6.1) respectively, although this was not statistically significant (p = 0.08). Median OS was longer for patients who received EE following prior ET + CDK4/6i. EE second-line following ET + CDK 4/6i vs ET alone resulted in median OS 37.7 months vs. 32.7 months (p = 0.449). EE third-line following ET + CDK4/6i vs prior ET alone resulted in median OS 59.2 months vs. 40.8 months (p < 0.010). This difference in OS was not statistically significant when indexed to the start of EE therapy. CONCLUSION: This study suggests that EE remains an effective treatment option after prior ET or ET + CDK4/6i use. Median TTNT of EE was longer for patients who received prior ET, whereas median OS was longer for patients who received prior ET + CDK4/6i. However, this improvement in OS was not statistically significant when indexed to the start of EE therapy suggesting that OS benefit is primarily driven by prior CDK4/6i use. EE remains an effective treatment option regardless of prior treatment option.

Hormone receptor-positive breast cancer and black race: does sex matter?

PURPOSE: Black breast cancer patients have worse clinical outcomes than their White counterparts. There are few studies comparing clinical outcomes between Black male breast cancer (MBC) and female breast cancer (FBC) patients. The objective of this study is to examine differences in presentation, treatment, and mortality between Black MBC and FBC. METHODS: The National Cancer Database was queried for all Black MBC and FBC patients, ages 18-90, with hormone receptor-positive breast cancer diagnosed between 2010 and 2016. Hormone receptor positivity was defined as estrogen receptor-positive, progesterone-positive and HER 2-negative cancer. Sociodemographic and clinical variables were compared between MBC and FBC patients on bivariable analysis. After propensity score matching, overall survival was evaluated using the log-rank test and Cox proportional hazards. RESULTS: Compared to FBC patients, MBC patients had higher rates of metastatic disease (stage 4, MBC 4.4% vs. FBC 2.6%, p < 0.001), larger tumors (tumor size < 2 cm, MBC 32.1 vs. FBC 49.1%, p < 0.001) and a higher percentage of poorly differentiated tumors (grade 3, MBC 28.5% vs. FBC 21.4%, p < 0.001). MBC patients had lower rates of hormone therapy (MBC 66.4% vs. FBC 80.7%, p < 0.001) and neoadjuvant chemotherapy (MBC 5.8% vs. FBC 7.5%, p = 0.05) than FBC. On propensity score matched analysis, Black MBC patients had a higher overall mortality (p25 of 60 months vs. 74 months) compared to FBC patients (p = 0.0260). CONCLUSION: Among hormone receptor-positive Black MBC and FBC patients, there are sex-based disparities in stage, hormone therapy use and overall survival.

Population-based analysis of non-operative management and treatment patterns in older women with estrogen receptor-positive breast cancer.

PURPOSE: To examine the proportion of older women with ER + HER2- breast cancer receiving non-operative management versus surgery, and to evaluate the use of axillary staging and adjuvant radiation in this population. METHODS: We queried the SEER database to identify all women aged 70 years or older with stage I-III ER + HER2- invasive breast cancer diagnosed between 2010 and 2016. We evaluated trends in non-operative management, breast surgery, axillary staging, and adjuvant radiation according to age at diagnosis. RESULTS: We identified 57,351 older women with ER + HER2- disease. Overall, 3538 (6.2%) of the cohort underwent non-operative management, 38,452 (67.0%) underwent breast-conserving surgery (BCS), and 15,361 (26.8%) underwent mastectomy. The proportion of patients undergoing non-operative management increased from 2.8% among 70-74-year-old women to 30.1% in those ≥ 90 years old (p < 0.001). In 53,813 women who underwent surgery, 36,850 (68.5%) underwent sentinel lymph node biopsy, while 10,861 (20.2%) underwent axillary lymph node dissection. Subgroup analysis of 29,032 older women undergoing BCS for stage I ER + HER2- breast cancer revealed a 14.2% rate of omission of axillary staging, increasing from 5.3% in those 70-74 years to 67.6% in those ≥ 90 years old (p < 0.001). Receipt of adjuvant radiation occurred in 63.3% of older women following BCS and 18% post-mastectomy, with similar trends towards omission in older age groups. CONCLUSION: Primary breast surgery remains the dominant management strategy for the majority of older women with ER + HER2- breast cancer. Omission of axillary staging and adjuvant radiation are used in a minority of eligible women undergoing breast conservation for early-stage disease.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

BACKGROUND/AIM: We aimed to evaluate the efficacy of fulvestrant and affecting clinical factors, including the optimal sequencing of fulvestrant and chemotherapy in a real-life cohort. METHODS: The data of 256 metastatic hormone-positive breast cancer patients treated with fulvestrant were evaluated. The association of clinical factors with survival was analyzed with Kaplan-Meier and Cox-regression analyses. RESULTS: The median age of patients was 57 years. More than half of the patients used fulvestrant in later lines and after chemotherapy (75.8%). The median progression-free (PFS) and overall survival (OS) of all cohort were 6.05+/-0.56 and 29.70+/-1.61 months, respectively. Primary endocrine resistance (HR: 1.989, 95% CI: 1.430-2.766, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p=0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p=0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p=0.340), disease control rate (p=0.076), and OS (p=0.289) and PFS (p=0.276) were similar to overall cohort. CONCLUSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

Efficacy and toxicity of extended aromatase inhibitors after adjuvant aromatase inhibitors-containing therapy for hormone-receptor-positive breast cancer: a literature-based meta-analysis of randomized trials.

BACKGROUND: Endocrine therapy with aromatase inhibitors (AIs) is the cornerstone of adjuvant systemic treatment for postmenopausal patients with hormone receptor-positive breast cancer. It has become clear that hormone receptor-positive breast cancer carries a consistent risk of relapse up to 15 years after diagnosis. Extended duration of adjuvant AIs therapy after completing initial standard adjuvant AIs-containing therapy may prevent late recurrence and death. We performed a meta-analysis to assess the real impact of the extended adjuvant therapy with AIs. METHODS: A literature-based meta-analysis of the randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, Embase, Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. The endpoints were disease-free survival (DFS), overall survival (OS), local recurrence, distant recurrence, contralateral breast cancer, non-breast cancer-related death, and toxicity. RESULTS: Eight trials comprising 15,966 patients met the inclusion criteria. The pooled analysis revealed a significant improvement in DFS (RR = 0.79; 95% CI 0.68-0.91), distant recurrence (RR = 0.75; 95% CI 0.58-0.96), and contralateral breast cancer (RR = 0.53; 95% CI 0.40-0.70) in the extended AIs group. While there was not significant improvement in OS (RR = 1.00, 95% CI 0.99-1.01), non-breast cancer-related death (RR = 1.16, 95% CI 0.96-1.41), and local recurrence (RR = 0.82; 95% CI 0.64-1.06), the subgroup analysis showed that the patient with tumor size > 2 cm (HR = 0.74, RD = - 0.31, P = 0.05 vs. HR = 0.85, RD = - 0.16, P = 0.20), node positive status (HR = 0.77, RD = - 0.27, P = < 0.0001 vs. HR = 0.89, RD = -0.12, P = 0.19) and previous chemotherapy use (HR = 0.75, RD = - 0.29, P = 0.003 vs. HR = 0.91, RD = -0.10, P = 0.44) would get a greater DFS benefit with extended AIs. Longer treatment with AIs was associated with an increased risk ratio of bone pain (RR = 1.26, RD = 0.04, P = 0.003), bone fractures (RR = 1.59, RD = 0.02, P = 0.002), osteoporosis (RR = 1.53, RD = 0.07, P = 0.005), myalgia (RR = 1.26, RD = 0.04, P = 0.02), and treatment discontinuation for adverse events (RR = 1.51, RD = 0.06, P = 0.0009). CONCLUSION: After initial standard AIs-containing adjuvant therapy, extended AIs therapy could further bring a DFS benefit for postmenopausal patients with early breast cancer, especially in the patients with high-risk characteristics.

Use of neoadjuvant versus adjuvant chemotherapy for hormone receptor-positive breast cancer: a National Cancer Database (NCDB) study.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is a well-established therapeutic option for patients with locally advanced disease often allowing downstaging and facilitation of breast conserving therapy. With evolution of better targeted treatment regimens and awareness of improved outcomes for significant responders, use of NAC has expanded particularly for triple negative and HER2-positive (HER2+) breast cancer. In this study, we explore utility of neoadjuvant chemotherapy for hormone receptor-positive HER2-negative (HR+ HER2-) patients. METHODS: Patients with HR+ HER2- breast cancer treated with chemotherapy before or after surgery were identified from 2010 to 2015 in the NCDB. Multivariable regression models adjusted for covariates were used to determine associations within these groups. RESULTS: Among 134,574 patients (clinical stage 2A, 64%; 2B, 21%; 3, 15%), 105,324 (78%) had adjuvant chemotherapy (AC) and 29,250 (22%) received NAC. Use of NAC increased over time (2010-2015; 13.2-19.4% and PR = 1.34 for 2015; p < 0.0001). Patients were more likely to receive NAC with cT3, cT4, and cN+ disease. Patients less likely to receive NAC were age ≥ 50, lobular carcinoma, increased Charlson-Deyo score, and government insurance. Complete response (pCR) was noted in 8.3% of NAC patients. Axillary downstaging occurred in 21% of patients, and predictors included age < 50 years, black race, poorly differentiated grade, invasive ductal histology, and either ER or PR negativity. CONCLUSIONS: NAC use among HR+ HER2- breast cancer patients has expanded over time and offers downstaging of disease for some patients, with pCR seen in only a small subset, but downstaging of the axilla in 21%. Further analysis is warranted to determine the subgroup of patients with HR+ HER2- disease who benefit from this approach.

Rationally Designed Ruthenium Complexes for Breast Cancer Therapy.

Since the discovery of the anticancer potential of ruthenium-based complexes, several species were reported as promising candidates for the treatment of breast cancer, which accounts for the greatest number of new cases in women every year worldwide. Among these ruthenium complexes, species containing bioactive ligand(s) have attracted increasing attention due to their potential multitargeting properties, leading to anticancer drug candidates with a broader range of cellular targets/modes of action. This review of the literature aims at providing an overview of the rationally designed ruthenium-based complexes that have been reported to date for which ligands were carefully selected for the treatment of hormone receptor positive breast cancers (estrogen receptor (ER+) or progesterone receptor (PR+)). In addition, this brief survey highlights some of the most successful examples of ruthenium complexes reported for the treatment of triple negative breast cancer (TNBC), a highly aggressive type of cancer, regardless of if their ligands are known to have the ability to achieve a specific biological function.

Relationship of pathological features and a 21 gene expression assay in younger versus older women with node-negative endocrine receptor-positive breast cancer.

PURPOSE: Determining the need for adjuvant chemotherapy in estrogen receptor (ER)+ disease can be influenced by pathological characteristics and gene expression assays [i.e., Oncotype Dx recurrence scores (RSs)]. The primary objective of this study is to investigate the relationship between the RSs and pathological markers in younger (< 50) versus older (≥ 50) women with early-stage node-negative ER+ breast cancer. METHODS: This was a single academic-center retrospective cohort study. Subjects who underwent Oncotype gene expression testing were retrospectively and sequentially identified. 436 Subjects were identified of which 344 were eligible for analysis (133 younger subjects < 50 years of age, and 211 older subjects ≥ 50 years). Pathological data assessed included the progesterone receptor (PR), histological grade (grade), Ki-67, and P53. A multivariable regression analysis was performed using age, PR, and grade as predictor variables for RS. Adjusted R2 was determined. To investigate the primary objective, subjects were stratified based on age, PR, and grade status in that sequence. Within each tumor subtype as determined by PR and grade statuses, the RSs in the younger versus older age group were compared using Student's t-test and the differences in the 95% confidence interval limits in RS means calculated. Age influence on adjuvant chemotherapy recommendation was also assessed by stratifying subjects based on age (< 50 vs. ≥ 50) and then by RS risk group (≤ 10, 11-25, ≥ 26). Subsequently, the proportions of younger versus older subjects within identical RS risk groups who were explicitly advised by their oncologist to proceed with chemotherapy as documented in their electronic health records were compared using χ2 test. RESULTS: Based on the multivariable regression analysis, the adjusted R2 was 0.229232 and RS was found to be independent of age (p = 0.7169). Between younger and older subjects with tumors with similar PR and grade pathological features, the differences in the RS were insignificant (p > 0.05). Chemotherapy was recommended in younger versus older women, in 0% when the RS was ≤ 10, 39% and 40% when the RS was 11-25 (p = 0.82), and 100% and 98% when the RS was ≥ 26 (p = 0.51), respectively. CONCLUSIONS: The relationship between pathological features and RS is consistent irrespective of age; therefore, models predicting RS may be applicable irrespective of age.

Utilization, duration, and outcomes of neoadjuvant endocrine therapy in the United States.

PURPOSE: To evaluate if real-world utilization of neoadjuvant endocrine therapy (NET) is associated with similar rates of response and breast conservation surgery (BCS) compared to neoadjuvant chemotherapy (NAC). METHODS: Our population-based assessment used the National Cancer Data Base to identify women diagnosed with stage II-III, hormone receptor (HR)-positive BC who underwent surgery and received endocrine therapy from 2004 to 2014. Women were categorized by receipt of NET, NAC or no neoadjuvant therapy. We used logistic regression to assess differences in outcomes between therapies using inverse propensity score weighting to adjust for potential selection bias. RESULTS: In our sample of 211,986 women, 6584 received NET, 52,310 received NAC, and 153,092 did not receive any neoadjuvant therapy. After adjusting for multiple relevant covariates and cofounders, there was no significant difference between NET and NAC with regard to BCS [odds ratio (OR) 0.91; 95% confidence interval (CI) (0.82-1.01)]; however, women who received NET were significantly less likely to achieve pCR [OR 0.34; 95% CI (0.23-0.51)] or a decrease in T stage [OR 0.39; CI (0.34-0.44)] compared to women treated with NAC. Patients who received NET for ≥ 3 months had higher odds of BCS (OR 1.59; 95% CI 1.46-1.73) and downstaging (OR 1.79; 95% CI 1.63-1.97) compared to patients who did not receive neoadjuvant therapy. CONCLUSIONS: Women who received NET had similar rates of BCS compared to women who received NAC. Those who received NET for longer treatment durations had increased odds of BCS and downstaging compared to women who did not receive neoadjuvant therapy.

Acceptance of adjuvant chemotherapy recommendations in early-stage hormone-positive breast cancer.

BACKGROUND: The role of systemic chemotherapy in early-stage, estrogen receptor (ER)-positive, and Her2-negative breast cancer remains an area of active investigation. The decision to recommend chemotherapy is multifactorial, and some patients decline recommended chemotherapy. We sought to identify patient factors leading to refusal of adjuvant therapy. MATERIALS AND METHODS: Data were collected from National Comprehensive Cancer Network Outcomes database and used to identify patients with primary, unilateral, T1-T2, N0, ER+, Her2-disease diagnosed from 2005-2011. Patient and clinical characteristics were analyzed for associations with physician recommendation for chemotherapy and patient acceptance of chemotherapy. A logistic regression model was used to identify patient and tumor characteristics associated with recommendation for and acceptance of chemotherapy. RESULTS: A total of 329 patients were identified. Chemotherapy was recommended in 191 patients (58.1%) and not in 138 (41.9%). Young age (odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.2-12.7), large tumor size (6.69, 95% CI: 3.31-13.5), and high Oncotype DX scores (11.2, 95% CI: 4.5-27.9) were more likely to receive a recommendation. About 71 patients (37.1%) refused chemotherapy. Patients younger than age 50 (20.9, 95% CI: 2.5-172.0), larger tumor size (3.4, 95% CI: 1.3-8.7), Oncotype DX score > 31 (31.3, 95% CI: 3.3-295.0), privately insured (8.2, 95% CI: 1.9-34.7), and Hispanic ethnicity (5.2, 95% CI: 1.6-16.8) were more likely to accept chemotherapy. CONCLUSIONS: Physician recommendations for adjuvant chemotherapy for early-stage ER + breast cancer varied by commonly considered factors. Patient acceptance varied by similar factors but was also influenced by race and insurance status. This may be explained by cultural or social factors not well understood or not overcome by physician guidance.

The Effect of C-Reactive Protein/Lymphocyte Ratio (CLR) on PFS in Metastatic Breast Cancer Patients Treated with CDK4/6 Inhibitors: A Novel Biomarker.

Objective: Hormone positive breast cancer is a tumor with high mortality. Combining antihormonal therapy with cyclin dependent kinase 4/6 inhibitors (CDK4/6i) has resulted in longer survival. The effect of inflammatory parameters such as c-reactive protein and c-reactive protein/lymphocyte ratio (CLR) on efficacy and survival in CDK4/6i treatment is unknown. In our study, we aimed to investigate the role of CLR and some parameters in predicting progression-free survival (PFS) with CDK4/6i. Methods: This retrospective cohort study included 78 patients with denovo and recurrent metastatic breast cancer treated with CDK4/6i. Cut off values for the prediction of mortality by various numerical parameter scores were performed by ROC Curve analysis. The effect of clinical variables, inflammatory and histopathological parameters on survival was analyzed by Kaplan-Meier method. Results: Neutrophil/lymphocyte ratio (NLR) and CLR were statistically significant in predicting mortality (p < 0.05). Ki67 and CLR were correlated with PFS. Age and CLR were correlated with OS (p < 0.05). CLR was statistically significant for both PFS (p = 0.022) and OS (p = 0.006). Conclusion: In patients with metastatic hormone-positive breast cancer using CDK4/6i, low CLR and low Ki67 were correlated with longer PFS duration.